Michael L. Boninger

Humans perform a variety of complex hand movements to manipulate objects, requiring precise control of changing forces. Understanding the role of sensorimotor cortex and the cortical dynamics underlying these actions is crucial for developing interventions that restore dexterous hand function after injury or disease. In this study, two male individuals with tetraplegia resulting from cervical spinal cord injury attempted a series of isometric grasps. Neural activity was recorded from the motor and somatosensory cortices using intracortical microelectrode arrays while participants attempted to exert a static or ramping force up and down. Despite their inability to execute movement and limited afferent input, the spiking activity in motor and somatosensory cortex was modulated with the task. Within the neural response, we identified independent neural modes—distinct patterns of population-level neural activity that were informative about both the timing and magnitude of the attempted force. Moreover, distinct neural modes were observed during static and dynamic grasping conditions, suggesting independent control schemes for maintaining and changing forces. These modes were related to phases of the task, including the onset, offset, holding periods, as well as increasing and decreasing attempted forces. These results will inform the design of intracortical brain–computer interface (iBCI) systems that can leverage the patterns of grasp and force control evident in sensorimotor cortex during attempted movement to restore dexterous hand function.

Intracortical microstimulation (ICMS) of somatosensory cortex can restore a sense of touch to people with spinal cord injury. In this early feasibility clinical trial (NCT01894802), we evaluated the safety, efficacy, and longevity of ICMS because there is a paucity of such long-term studies in humans. This information is crucial to the development of clinical neuromodulation devices, particularly for restoring touch, hearing, and vision. ICMS was delivered to five participants with spinal cord injury who were each implanted with two Blackrock NeuroPort microelectrode arrays in the hand representation of Brodmann's area 1. Across implant durations spanning 2 to 10 years, we measured single-electrode detection thresholds, projected fields, quality reports, and electrode health characteristics. ICMS-related adverse events were documented throughout. More than 168 million ICMS pulses were delivered across a combined implant duration of 27 years without any serious adverse events or direct negative effects on electrode health. ICMS consistently evoked sensations localized to the hand. Rarely, sensations persisted for brief periods after stimulation offset (3 to 25 events across participants). ICMS detection thresholds increased slowly over time (about 3.5 microamperes per year), but 64 ± 13% of the electrodes still reliably evoked tactile sensations (about 21% decrease in functional electrodes), including 60% of the electrodes after 10 years in one participant. The quality and projected field coverage of ICMS-evoked sensations were both consistent. Delivering ICMS to the somatosensory cortex was safe and effective, consistently evoking informative somatosensory percepts as long as 10 years, demonstrating the clinical promise of ICMS for sensory restoration.

Humans perform a variety of complex hand movements to manipulate objects, requiring precise control of changing forces. Understanding the role of sensorimotor cortex and the cortical dynamics underlying these actions is crucial for developing interventions that restore dexterous hand function after injury or disease. In this study, two individuals with tetraplegia resulting from cervical spinal cord injury attempted a series of isometric grasps. Neural activity was recorded from the motor and somatosensory cortices using intracortical microelectrode arrays while participants attempted to exert a static force or to ramp force up and down. Despite their inability to execute movement, and with limited afferent input, the spiking activity in motor and somatosensory cortex was modulated with the task. Within the neural response we identified independent neural modes - distinct patterns of population-level neural activity - that were informative about both the timing and magnitude of the force. Moreover, distinct neural modes were observed during static and dynamic grasping conditions, suggesting independent control schemes for maintaining and changing forces. These modes were related to phases of the task, including the onset, offset, holding periods, as well as phases of increasing and decreasing force. These results will inform the design of intracortical brain-computer interface (iBCI) systems that can leverage these naturally occurring patterns of grasp and force control to restore dexterous hand function. Significance Statement: Restoring dexterous hand function after injury remains a major challenge, partly due to an incomplete understanding of the cortical dynamics underlying grasping and force control. In this study, we investigated neural activity within the motor and somatosensory cortices of individuals with tetraplegia attempting to perform grasps to different target forces with varying temporal profiles. We identified distinct neural modes modulated during specific phases of grasp that encode force information throughout the task. These findings suggest that brain-computer interfaces could leverage these native neural modes to restore grasping and force modulation.

Background: Intracortical microstimulation (ICMS) of somatosensory cortex can restore a sense of touch to people with spinal cord injury (SCI). In this early-feasibility clinical trial, we evaluate the safety, efficacy, and longevity of ICMS as there is a paucity of such long-term studies in humans. This information is crucial to the development of clinical neuromodulation devices, particularly for restoring touch, hearing, and vision. Methods: ICMS was delivered to five participants with SCI who were each implanted with two Blackrock NeuroPort microelectrode arrays in the hand representation of Brodmann’s Area 1. Across implant durations spanning two to ten years, we measured single-electrode detection thresholds, projected fields, quality reports, and electrode health characteristics. ICMS-related adverse events were documented throughout. Results: Over 168 million ICMS pulses were delivered across a combined implant duration of 24 years without any serious adverse events or direct negative effects on electrode health. ICMS consistently evoked sensations localized to the hand. Rarely, sensations persisted for brief periods after stimulation offset (3–25 events across participants). ICMS detection thresholds increased slowly over time (∼3.5 μA/year), but 62±15% of the electrodes still reliably evoke tactile sensations (∼25% decrease in functional electrodes), including 55% of the electrodes after 10 years in one participant. The quality and projected field coverage of ICMS-evoked sensations were both consistent. Conclusions: Delivering ICMS to somatosensory cortex was safe and reliable, consistently evoking informative somatosensory percepts as long as 10 years, demonstrating the clinical promise of ICMS for sensory restoration. (Funded by NIH; ClinicalTrials.gov: NCT01894802 ).

Objective. Intracortical microstimulation (ICMS) of human somatosensory cortex evokes tactile percepts that people describe as originating from their own body, but are not always described as feeling natural. It remains unclear whether stimulation parameters such as amplitude, frequency, and spatiotemporal patterns across electrodes can be chosen to increase the naturalness of these artificial tactile percepts. Approach. In this study, we investigated whether biomimetic stimulation patterns—ICMS patterns that reproduce essential features of natural neural activity—increased the perceived naturalness of ICMS-evoked sensations compared to a non-biomimetic pattern in three people with cervical spinal cord injuries. All participants had electrode arrays implanted in their somatosensory cortices. Rather than qualitatively asking which pattern felt more natural, participants directly compared natural residual percepts, delivered by mechanical indentation on a sensate region of their hand, to artificial percepts evoked by ICMS and were asked whether linear non-biomimetic or biomimetic stimulation felt most like the mechanical indentation. Main results. We show that simple biomimetic ICMS, which modulated the stimulation amplitude on a single electrode, was perceived as being more like a mechanical indentation reference on 32% of the electrodes. We also tested an advanced biomimetic stimulation scheme that captured more of the spatiotemporal dynamics of cortical activity using co-modulated stimulation amplitudes and frequencies across four electrodes. Here, ICMS felt more like the mechanical reference for 75% of the electrode groups. Finally, biomimetic stimulus trains required less charge than their non-biomimetic counterparts to create an intensity-matched sensation. Significance. We conclude that ICMS encoding schemes that mimic naturally occurring neural spatiotemporal activation patterns in the somatosensory cortex feel more like an actual touch than non-biomimetic encoding schemes. This also suggests that using key elements of neuronal activity can be a useful conceptual guide to constrain the large stimulus parameter space when designing future stimulation strategies. This work is a part of Clinical Trial NCT01894802.

Microstimulation of the somatosensory cortex can evoke tactile percepts in people with spinal cord injury, providing a means to restore touch. While location and intensity can be reliably conveyed, two issues that prevent creating more complex naturalistic sensations are a lack of methods to effectively scan the large stimulus parameter space and difficulties with assessing percept quality. Here, we address both challenges with an experimental paradigm that enables three male individuals with tetraplegia to control their stimulation parameters in a blinded fashion to create sensations for different virtual objects. Using this method, participants can reliably create object-specific sensations and report vivid object-appropriate characteristics. Moreover, both linear classifiers and participants can match stimulus profiles with their respective objects significantly above chance without any visual cues. Confusion between two sensations increases as the associated objects share more tactile characteristics. We conclude that while visual information contributes to the experience of the artificially evoked sensations, microstimulation in the somatosensory cortex itself can evoke intuitive percepts with a variety of tactile properties. This self-guided stimulation approach may be used to effectively characterize percepts from future stimulation paradigms.

Objective: The notion of a somatotopically organized motor cortex, with movements of different body parts being controlled by spatially distinct areas of cortex, is well known. However, recent studies have challenged this notion and suggested a more distributed representation of movement control. This shift in perspective has significant implications, particularly when considering the implantation location of electrode arrays for intracortical brain–computer interfaces (iBCIs). We sought to evaluate whether the location of neural recordings from the precentral gyrus, and thus the underlying somatotopy, has any impact on the imagery strategies that can enable successful iBCI control. Approach: Three individuals with a spinal cord injury were enrolled in an ongoing clinical trial of an iBCI. Participants had two intracortical microelectrode arrays implanted in the arm and/or hand areas of the precentral gyrus based on presurgical functional imaging. Neural data were recorded while participants attempted to perform movements of the hand, wrist, elbow, and shoulder. Main results: We found that electrode arrays that were located more medially recorded significantly more activity during attempted proximal arm movements (elbow, shoulder) than did lateral arrays, which captured more activity related to attempted distal arm movements (hand, wrist). We also evaluated the relative contribution from the two arrays implanted in each participant to decoding accuracy during calibration of an iBCI decoder for translation and grasping tasks. For both task types, imagery strategy (e.g. reaching vs wrist movements) had a significant impact on the relative contributions of each array to decoding. Overall, we found some evidence of broad tuning to arm and hand movements; however, there was a clear bias in the amount of information accessible about each movement type in spatially distinct areas of cortex. Significance: These results demonstrate that classical concepts of somatotopy can have real consequences for iBCI use, and highlight the importance of considering somatotopy when planning iBCI implantation.